EP 0 305 787 A1 discloses a permselective asymmetric membrane suitable for hemodialysis, hemodiafiltration and hemofiltration of blood, comprised of a hydrophobic first polymer, e.g. polyamide, a hydrophilic second polymer, e.g. polyvinylpyrrolidone, and suitable additives. The membrane has a three-layer structure, comprising a first layer in the form of dense, rather thin skin, responsible for the sieving properties, a second layer in the form of a sponge structure, having a high diffusive permeability and serving as a support for said first layer, and a third layer in the form of a finger structure, giving the membrane mechanical stability.
WO 2004/056459 A1 discloses a permselective asymmetric membrane suitable for hemodialysis, comprising at least one hydrophobic polymer, e.g. polyethersulfone, and at least one hydrophilic polymer, e.g. polyvinylpyrrolidone. The outer surface of the hollow fiber membrane has pores in the range of 0.5-3 μm and the number of pores in the outer surface is in the range of 10,000 to 150,000 pores per mm2.
While these membranes already show very good performance in hemodialysis and excellent biocompatibility, there is a desire to further improve their performance to enhance removal of middle molecular weight substances, e.g. inflammatory mediators having a molecular weight between 20 and 40 kDa. It has now been found that membranes with improved performance can be obtained by modifying the surface of the membranes with particular compounds selected from the group consisting of hyaluronic acid and copolymers of 2-methacryloyloxyethyl phosphoryl choline and other vinyl polymerizable monomers. Modification of various types of membranes with hyaluronic acid or phosphoryl choline analogs in order to improve biocompatibility has been reported:
KR 2005/094968 discloses hollow fiber membranes having an inner surface comprising 0.01 to 5 wt.-% hyaluronic acid or its derivatives. The inner coagulation solution used for production of the hollow fiber membranes comprises 0.1 to 20 wt.-% hyaluronic acid or its derivatives. In the list of polymers suitable for the membrane, polysulfone, polyethersulfone (PES), and polyacrylonitrile (PAN) are mentioned among others. According to the reference, the membrane prevents blood coagulation.
KR 2005/078748 discloses hollow fiber membranes comprising 0.01 to 2 wt.-% hyaluronic acid or its derivatives. The spinning dope used for production of the hollow fiber membranes comprises 0.01 to 5 wt.-% hyaluronic acid or its derivatives. In the list of polymers suitable for the membrane, polysulfone, PES, and PAN are mentioned among others. According to the reference, the membrane shows consistent blood compatibility.
WO 2008/041183 discloses electrospun microtubes comprising a shell and a coat over an internal surface of the shell.
In the list of polymers suitable for the shell, polyamide, PVP, PAN are mentioned among others. In the list of suitable polymers for the coat, hyaluronic acid is mentioned.
JP 2008/093154 A discloses a medical device for sustained release of drugs comprising hollow fibers. The micropores of the hollow fibers are filled with a water-soluble polymer having a larger molecular weight than the cut-off molecular weight of the membrane. In the list of polymers suitable for the membrane, polysulfone, PES, PAN and polyamide are mentioned among others. Hyaluronic acid is mentioned among the preferred water-soluble polymers for filling the micropores.
JP 2003/320229 A discloses hollow fiber membranes made mainly of polysulfone comprising, in the inner surface, a copolymer of a vinyl polymerizable monomer having a zwitterion in the molecule and another vinyl polymerizable monomer. Phosphobetaines, sulfobetaines and carboxybetaines are mentioned, sulfobetaines being preferred. In the list of polymers suitable for the membrane, polysulfone, PES, PAES, and polyarylate polyethersulfone are mentioned. A polybetaine having a molecular weight ≦5,000 Da is dissolved in the bore liquid at a concentration of 0.001 to 10 wt.-%, preferably 0.01 to 5 wt.-%. According to the reference, the membrane shows low protein absorption and good biocompatibility.
US 2004/0045897 A (WO 02/09857) discloses hollow fiber membranes having a copolymer of 2-methacryloyloxyethylphosphorylcholine (MPC) and another vinyl polymerizable monomers on a surface of the membrane. The comonomers are selected from vinylpyrrolidone, styrene, and (meth)acrylate derivatives. The polybetaine is dissolved in the bore liquid or the coagulation bath at a concentration of 0.001 to 10 wt.-%, preferably 0.01 to 5 wt.-%. In the list of polymers suitable for the membrane, polysulfone, PES, PAES, polyallylate polyethersulfone, polyamide, and PAN are mentioned. According to the reference, the membrane activates thrombocytes very slightly.
Biomaterials 22/3 (2001) 243-251 discloses a polymer blend of polysulfone and MPC (7 and 15 wt.-%, respectively). The reference reports that the permeability of the membrane for solute having a molecular weight below 20 kDa increased with the addition of MPC, while the permeability of lowmolecular-weight protein (molecular weight 12 kDa) did not change.
J. Membr. Sci. 249 (2005) 133-141 discloses the modification of cellulose acetate hollow fiber membranes with a copolymer of butyl acrylate and MPC. The copolymer is used in the inner coagulation solution.
J. Membr. Sci. 305 (2007) 279 discloses the modification of EVOH hollow fiber membranes with phosphoryl choline groups.
However, no mention is made in the documents of an increased selectivity of the membrane, as compared to unmodified membranes. No values for hydraulic permeability are given.